The National Institutes of Health (NIH) is the nation?s leading medical research agency and the primary Federal agency whose mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability, conducting, supporting and making medical discoveries that improve people?s health and save lives. The National Institute of Neurological Disorders and Stroke (NINDS) is a part of the National Institutes of Health (NIH), conducting research into the causes, treatment, and prevention of neurological disorders and stroke. The NINDS mission is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. The NlNDS currently has planned two (2) trials; a Phase 1 safety trial and a Phase 2 proof of concept trial assessing the safety and efficacy profiles of intranasally instilled rhE-selectin. The patients in these trials will be diagnosed with Binswanger Disease, involving progressive impairment of cognition. The progressive cognitive impairment derives from a stroke like etiology. The illness begins with impairments of gait and balance, focal neurologic findings, and executive dysfunction. The disorder is progressive and leads to further lacunar recurrent strokes with increasing functional disability that is both motor and cognitive. Despite the use of antithrombotic drugs for the prevention of recurrent strokes, 10% of patients who experience any cerebral ischemic event will go on to have a stroke within 90 days. The development of new treatment strategies for prevention of the various forms of recurrent stroke is an important issue for modern medicine. The principle for the use of E-selectin is the increasing evidence that a state of chronic, subtle immune dysregulation that leads to inflammation at the sites of endothelial activation plays an important role in the pathogenesis of strokes. Control of such molecular inflammation at the sites of endothelial activation can be achieved by induction of mucosal tolerance. The induction of mucosal tolerance by repeated low-dose intranasal administration of E-selectin causes a shift of the immune response. T -cells tolerized to E-selectin become circulating regulatory cells that release anti-inflammatory, immunosuppressive cytokines locally when these T-cells encounter E-selectin in activated blood vessel segments. The local release of these cytokines suppresses the vessel activation and prevents local thrombosis or hemorrhage. This approach to stroke prevention differs from conventional measures. It will very likely synergize with existing clinical regimens for prevention of stroke and will stimulate a great deal of research in this under-explored area.